Interaction of SOCS3 with NonO attenuates IL-1beta-dependent MUC8 gene expression.
The intracellular negatively regulatory mechanism which affects IL-1beta-induced MUC8 gene expression remains unclear. We found that SOCS3 overexpression suppressed IL-1beta-induced MUC8 gene expression in NCI-H292 cells, whereas silencing of SOCS3 restored IL-1beta-induced MUC8 gene expression. Sequentially activated ERK1/2, RSK1, and CREB by IL-1beta were not affected by SOCS3, indicating that SOCS3 has an independent mechanism of action. Using immunoprecipitaion and nano LC mass analysis, we found that SOCS3 bound NonO (non-POU-domain containing, octamer-binding domain protein) in the absence of IL-1beta, whereas IL-1beta treatment dissociated the direct binding of SOCS3 and NonO. A dominant-negative SOCS3 mutant (Y204F/Y221F) did not bind to NonO. Interestingly, SOCS3 overexpression dramatically suppressed MUC8 gene expression in cells transfected with wild-type or siRNA of NonO. Moreover, silencing of SOCS3 dramatically increased NonO-mediated MUC8 gene expression caused by IL-1beta compared to NonO overexpression alone, suggesting that SOCS3 acts as a suppressor by regulating the action of NonO.
Song
Kyoung Seob
KS
The Airway Mucus Institute, Yonsei University College of Medicine, Seoul, Republic of Korea.
Kim
Kyubo
K
Chung
Kwang Chul
KC
Seol
Jae Hong
JH
Yoon
Joo-Heon
JH
D002460:Cell Line; D004268:DNA-Binding Proteins; D015870:Gene Expression; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism*; D009077:Mucins / Q000235:genetics*; D034521:Nuclear Matrix-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D050810:Octamer Transcription Factors / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D054875:Ubiquitination
D004268:DNA-Binding Proteins; D053583:Interleukin-1beta; C105059:MUC8 protein, human; D009077:Mucins; C083214:NONO protein, human; D034521:Nuclear Matrix-Associated Proteins; D050810:Octamer Transcription Factors; D016601:RNA-Binding Proteins; C106644:SOCS3 protein, human; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins